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360 Part V: Therapeutic Principles Chapter 23: Hematopoietic Cell Transplantation 361

complete donor type. Most reports suggest that persistent mixed chi- TABLE 23–2. Topics Addressed During Counseling
merism is a significant risk factor for disease relapse. 185,186 Interventions
such as withdrawal of immunosuppressive medications, CD34-selected Meetings with Transplant Candidate and Care Provider
donor cell boost, and DLI have been used to convert mixed chimerism I. Rationale for why transplantation is a therapeutic option
to complete donor type, although these interventions are not without II. How the transplantation is performed
risk and can precipitate GVHD. A significant percentage of patients Autologous
who received alemtuzumab-containing conditioning regimens required Allogeneic—choice for full-dose versus RIC
DLI to promote donor engraftment and protect against immune-
mediated graft rejection, but the risk of developing post-DLI GVHD III. Source of cells
was significant. Mixed chimerism is not unique to RIC; prior to the Marrow versus blood versus other source
187
addition of ATG, almost 60 percent of patients who received high-dose IV. Risks of procedure
conditioning and allogeneic HCT for severe aplastic anemia had mixed V. Graft failure and graft rejection
chimerism, of whom two-thirds eventually converted to complete donor VI. Risk of GVHD
hematopoiesis while the remainder experienced late graft failure. 188
Persistent mixed chimerism may have a role in allogeneic trans- Acute and chronic forms, compatibility of graft
plantation for noncancer patients. In organ transplantation, tolerance, Likelihood for long-term immune suppression medication
defined as immunosuppressive drug withdrawal without graft rejection, VII. Nonrelapse mortality at 100 days and 1 year
was achieved in kidney transplant recipients who received the same VIII. Risks of relapse
donor marrow when sustained mixed chimerism was established, and IX. Timing of transplant
not in recipients who experienced donor hematopoietic graft loss. 189 X. Projected result
XI. Requirement for dedicated care provider
EVALUATION AND SELECTION OF XII. Other
CANDIDATES FOR TRANSPLANTATION Financial implications
Durable power of attorney
Most transplantation candidates are referred by hematologists or oncol- Banking of sperm, in vitro fertilized eggs
ogists to the tertiary center where HCT will be performed. Patients
considered for transplantation require in-depth evaluation and coun- Duration of stay near the transplantation center
seling by experienced transplantation physicians, nurses, and social Return to home and work
workers. A detailed review of initial diagnostic studies, previous drug Sexual activity
and radiation treatments, and responses to these interventions, as well Quality-of-life issues
as a psychosocial assessment of the patient and their caregivers, are of Habits such as smoking, alcohol, and drug addiction
the utmost importance. Table 23–2 highlights the issues and topics that
should be addressed during counseling meetings with transplantation GVHD, graft-versus-host disease; RIC, reduced-intensity conditioning.
candidates and their caregivers. Important factors which consistently
190
impact outcomes following HCT include, but are not limited to, dis-
ease status at transplantation, type and compatibility of donor, recipient outcomes compared to patients transplanted earlier in the course of
age, and comorbid medical conditions. Early referral for transplantation their disease and to those who have achieved good, albeit temporary,
consultation is critical, particularly if allogeneic HCT is under consider- control of their disease. On the other hand, attempts to salvage patients
ation, because of the time required to identify a suitable donor. with advanced disease who have failed multiple therapies are rarely
successful, and transplantation is often best considered early in the
DISEASE STATUS AT THE TIME OF course of therapy. These discussions are complex, as earlier transplan-
tation, especially allogeneic, carries significant risks to the patient. A
TRANSPLANTATION number of other disease-specific considerations are important in deter-
Disease status at the time of transplantation is perhaps the most pow- mining the appropriate timing for transplantation, including the pres-
erful predictor of long-term disease-free survival following allogeneic ence and/or persistence of cytogenetic and molecular abnormalities,
and autologous HCT. Early studies of allogeneic HCT were performed the immune phenotype, and evidence of extramedullary or extranodal
using predominantly patients with refractory and progressive disease. disease. Advanced genetic characterization of leukemia and lymphoma
191
Although a small percentage of these patients were salvaged, transplan- may provide improved insight into cohorts of patients for which HCT
tation was unsuccessful in the majority of patients due to progressive should be performed earlier in the course of disease.
malignancy. Patients with acute leukemias transplanted in complete
remission (CR) have substantially better outcomes compared to those
transplanted with active disease. Even very minimal amounts of AGE
192
residual disease are associated with significantly higher relapse risk Historically, older age was a significant barrier to allogeneic HCT, since
in patients undergoing allogeneic HCT for AML, regardless of condi- older patients suffered severe and often prohibitive toxicity after high-
tioning intensity, 193–195 underscoring the importance of disease status at dose conditioning regimens. However, the impact of older age is mit-
200
transplant as a prognostic factor. Likewise, disease status as determined igated by the increasing use of RIC for allogeneic HCT. High-dose
201
by positron emission tomography (PET) prior to transplant is an impor- conditioning and allogeneic HCT is generally reserved for patients 60
tant predictor of progression-free survival for patients with diffuse large years of age or younger, whereas allotransplantation with RIC has been
B-cell lymphoma and HL undergoing autologous HCT. 196–199 These sce- performed successfully in patients into their eighth decade of life. Most
narios highlight a truism: patients who have advanced poorly controlled centers in the United States do not have a stringent age cutoff for alloge-
disease at the start of transplant conditioning have significantly inferior neic HCT, although careful screening for comorbid medical conditions,

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